Hemin, heme oxygenase-1 inducer, attenuates immobilization-induced skeletal muscle atrophy in mice.

ABSTRACT

AIMS: The present study examined the effect of the heme oxygenase (HO)-1 inducer hemin on skeletal muscle atrophy induced by single limb immobilization in mice. MAIN METHODS: Immobilization was conducted in the left hindlimb of C57BL/6 mice for 1 week and the right hindlimb was used as a control. Hemin (30 mg/kg) was administered intraperitoneally once a day during the immobilization period. Gastrocnemius muscles were used for analysis. Muscle weight was measured to quantify degree of atrophy, and exhaustion treadmill test was performed to assess muscle function. KEY FINDINGS: Immobilization increased HO-1 protein levels in skeletal muscle, which was further increased by hemin treatment. Immobilization induced weight loss and a functional reduction in skeletal muscle, which were attenuated by hemin treatment. Gene expression and protein levels of MuRF1 and atrogin-1 were increased by immobilization and hemin treatment attenuated the increment. The phosphorylation of mTOR and p70S6k was decreased by immobilization in skeletal muscle and hemin had no effect on mTOR and p70S6k phosphorylation. Gene expression of the antioxidants superoxide dismutase and glutathione peroxidase 1 in skeletal muscle was reduced by immobilization and hemin treatment recovered the reduction. Immobilization increased levels of carbonylated protein and nitrotyrosine in skeletal muscle, which was reversed by hemin treatment. Gene expression of inflammatory cytokines was increased by immobilization and was normalized as a result of hemin treatment. SIGNIFICANCE: These results suggest that hemin attenuates immobilization-induced skeletal muscle atrophy through the suppression of protein degradation via its anti-oxidant and anti-inflammatory properties.